It is proposed to continue a thorough study of the accurate, precise and sensitive determination of N-nitrosamines of varying structures singly and in mixtures using differential pulse polarography. These studies will be conducted in pure aqueous solutions as well as biological fluids, such as blood serum, urine, gastric juice and tissue homogenates. Concurrent with the analytical study will be the application of differential pulse methods to the study of the effect of various agents on the inhibition of the metabolism of nitrosamines. Among the agents to be studied will be diethyldithiocarbamate, dimethylsulfoxide and enediols, such as ascorbic acid. In the latter instance model systems will be used prior to in vivo studies to investigate the interactions between enediols, nitrosamines and nitrite ion. The analytical method will also be applied to studies of the chemical properties on the N-nitroso group. In particular, the role of the N-nitroso group in enhancing the chemical activity of nearby groups will be investigated. As the analytical methods are further refined, especially for tissue homogenates, the possibility of the enzymatic decarboxylation of nitrososarcosine to yield dimethylnitrosamine will be examined. The main thrust in the study will be the development of an analytical method for both volatile and non-volatile nitrosamines applicable to a variety of media and suitable for single nitrosamines as well as mixtures. The direct application of these methods to important problems involving nitrosamines will establish the usefulness of the methods as well as to provide important information about the chemical and metabolic properties of nitrosamines.